Bifunctional Au@Bi₂Se₃ Core–Shell Nanoparticle for Synergetic Therapy by SERS‐Traceable AntagomiR Delivery and Photothermal Treatment

Abstract

Abstract For the first time, topological insulator bismuth selenide nanoparticles (Bi 2 Se 3 NP) are core–shelled with gold (Au@Bi 2 Se 3 ) i) to represent considerably small‐sized (11 nm) plasmonic nanoparticles, enabling accurate bioimaging in the near‐infrared region; ii) to substantially improve Bi 2 Se 3 biocompatibility, iii) water dispersibility, and iv) surface functionalization capability through straightforward gold–thiol interaction. The Au@Bi 2 Se 3 is subsequently functionalized for v) effective targeting of SH‐SY5Y cancer cells, vi) disrupting the endosome/lysosome membrane, vii) traceable delivery of antagomiR‐152 and further synergetic oncomiR knockdown and photothermal therapy (PTT). Unprecedentedly, it is observed that the Au shell thickness has a significant impact on evoking the exotic plasmonic features of Bi 2 Se 3 . The Au@Bi 2 Se 3 possesses a high photothermal conversion efficiency (35.5%) and a remarkable surface plasmonic effect (both properties are approximately twofold higher than those of 50 nm Au nanoparticles). In contrast to the siRNA/miRNA delivery methods, the antagomiR delivery is based on strand displacement, in which the antagomiR‐152 is displaced by oncomiR‐152 followed by a surface‐enhanced Raman spectroscopy signal drop. This enables both cancer cell diagnosis and in vitro real‐time monitoring of the antagomiR release. This selective PTT nanoparticle can also efficiently target solid tumors and undergo in vivo PTT, indicating its potential clinical applications.